Project Summary/Abstract Everyday people die unnecessarily from opioid overdose-related addiction. With each opioid prescription a patient?s risk for opioid misuse or abuse increases. With an estimated 56 million tablets of 5 mg hydrocodone annually prescribed after third molar extractions in the United States, 3.5 million young adults may be unnecessarily exposed to opioids by dentists who are increasing their patient?s risk for addiction. To provide health care professionals, including dentists, and their patients with the best possible evidence for clinical based decision making when deciding upon analgesics for acute post-surgical pain management, we propose a double blind, stratified randomized clinical trial to demonstrate a combination of over-the-counter non-opioid containing analgesics is not inferior to than the most commonly prescribed opioid analgesic. Patients will be randomized within each study site/clinic, and stratified based upon gender due to differences in prescribing patterns and pain tolerance. We will use the impacted 3rd molar extraction model due to the predictable severity of the post-operative pain and generalizability of results. Within each site/clinic and gender type (male/female), patients will be randomized to receive either OPIOID (hydrocodone/acetaminophen) or NON-OPIOID (ibuprofen/acetaminophen). Outcomes data include pain levels, adverse events, overall patient satisfaction, ability to sleep, and ability to perform daily functions. To develop clinical guidelines and a clinical decision making tool, pain management, extraction difficulty and number of tablets taken will be collected enabling an experimental decision making tool to be developed. The proposed methods address the short comings of other analgesic studies. Although prior studies have tested short-term effects of single doses of pain medications, patients and their dentists are interested in managing acute pain for the entire post-operative period, not just the first 12 hours. They care about their ability to perform their normal daily functions without feeling queasy or nauseous, and they care about their ability to sleep at night. Parents of young people also care about the risks of subsequent opioid use, either related to treatments received or to subsequent use of leftover pills, which we will capture with objective measures of subsequent opioid prescriptions using PDMP data. This study would be the first to address these short comings. Upon successful completion of our proposed pragmatic clinical trial, patients and their families will be better able to make informed decisions regarding what pain medication (opioid vs. non-opioid) will best manage their pain after a dental procedure and will have a better understanding of the potential risks associated with opioid prescriptions.